The two most abundant plasma proteins, IgG and albumin, are retained in the bloodstream with long half-lives (~3 weeks) due to intracellular salvage by the neonatal Fc receptor.  There have been significant clinical advances in therapy made for chronic diseases (hemophilia, diabetes, arthritis) by fusing therapeutics to FcRn-enabling ligands to prolong their pharmacokinetics.  The Glassman lab is extending this strategy to improve the pharmacologic profile of fibrinolytic enzymes and is carrying out studies to understand the underlying mechanisms governing how cargo drug properties impact the efficiency of this strategy.

Funding: R00HL153696

Red blood cells survive in the bloodstream for 3-4 months on average and present a massive surface area for drug loading.  We are working to better understand and optimize in vivo drug loading onto the erythrocyte surface.  This strategy is being implemented for a diverse array of therapeutics including: cytokine quenchers, pro-hemostatic drugs, and drug-loaded nanoparticles.

Nanocarriers are becoming an increasingly important part of the pharmacologic arsenal, including drug-loaded liposomes and RNA-containing lipid nanoparticles.  Despite decades of research in this area, the pharmacokinetic properties of the nanocarriers themselves are not well-studied.  We develop physiologically-based pharmacokinetic models to predict the blood and tissue kinetics of nanocarriers to generate testable hypotheses regarding the impact of nanocarrier properties on disposition and efficacy.